RESUMEN
The marine tunicate-derived Streptomyces albidoflavus RKJM0023 was cultured in the presence of a rhamnolipid mixture in an effort to elicit the production of silent natural products. MS/MS-based molecular networking analysis enhanced with nonparametric statistics highlighted the upregulation of a molecular cluster (Kruskal-Wallis p = 1.6 e-6 for 1) in which no MS/MS features had library matches. Targeted isolation of these features resulted in the discovery of nine new N-acylated lipopeptides, albubactins A-H (1-8) each containing a unique glutamine tripeptide and a C-terminal ethyl ester moiety. Three related albubactin acids A-C (9-11) lacking the ethyl ester were also identified. NMR spectroscopy and UPLC-HR-ESI-MS/MS demonstrated that the albubactins were obtained as mixtures that shared a common m/z and differed only in their acylated terminal groups. Due to the complex spectroscopic elucidation with many overlapping shifts, a total synthesis of albubactin A (1) was completed and used to determine the absolute configuration of the new albubactins.
Asunto(s)
Glucolípidos , Lipopéptidos , Streptomyces , Streptomyces/química , Glucolípidos/química , Glucolípidos/síntesis química , Lipopéptidos/química , Lipopéptidos/biosíntesis , Estructura Molecular , Animales , Resonancia Magnética Nuclear Biomolecular , Urocordados/química , Biología Marina , Espectrometría de Masas en TándemRESUMEN
Levesquamide A is an isothiazolinone-containing anti-tubercular natural product isolated from Streptomyces sp. RKND-216. Through the use of Global Natural Product Social Molecular Networking (GNPS), additional members of the levesquamide family were identified (B-G). Levesquamide B is a glycosylated analogue, isolated and structurally elucidated via spectroscopical techniques along with the putative structures of levesquamide C and D. For masses relating to the additional three levesquamides (E-G), their complete structures remain ambiguous.
Asunto(s)
Productos Biológicos , Streptomyces , Productos Biológicos/químicaRESUMEN
Four new cyclic decapeptides, auyuittuqamides A-D (1-4), were obtained from Sesquicillium microsporum RKAG 186 obtained from marine sediment collected from the intertidal zone of Frobisher Bay, Nunavut, Canada. The structures of the compounds were elucidated by NMR spectroscopy and tandem mass spectrometry. The absolute configurations of the amino acids were determined using Marfey's method.
Asunto(s)
Aminoácidos/química , Hypocreales/química , Péptidos Cíclicos/química , Streptomyces/química , Bahías , Canadá , Espectroscopía de Resonancia Magnética , Biología Marina , Estructura Molecular , Péptidos Cíclicos/aislamiento & purificación , Espectrometría de Masas en Tándem/métodosRESUMEN
Four new cyclic heptapeptides, mortiamides A-D (1-4), were obtained from a novel Mortierella sp. isolate obtained from marine sediment collected from the intertidal zone of Frobisher Bay, Nunavut, Canada. The structures of the compounds were elucidated by NMR spectroscopy and tandem mass spectrometry. The absolute configurations of the amino acids were determined using Marfey's method. Localization of l and d amino acids within each compound was ascertained by retention time comparison of the partial hydrosylate products of each compound to synthesized dipeptide standards using LC-HRMS. Compounds 1-4 did not exhibit any significant antimicrobial or cytotoxic activity.
Asunto(s)
Mortierella/química , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacología , Bahías , Canadá , Ensayos de Selección de Medicamentos Antitumorales , Biología Marina , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Péptidos Cíclicos/químicaRESUMEN
Natural products are a crucial source of antimicrobial agents, but reliance on low-resolution bioactivity-guided approaches has led to diminishing interest in discovery programmes. Here, we demonstrate that two in-house automated informatic platforms can be used to target classes of biologically active natural products, specifically, peptaibols. We demonstrate that mass spectrometry-based informatic approaches can be used to detect natural products with high sensitivity, identifying desired agents present in complex microbial extracts. Using our specialised software packages, we could elaborate specific branches of chemical space, uncovering new variants of trichopolyn and demonstrating a way forward in mining natural products as a valuable source of potential pharmaceutical agents.
Asunto(s)
Productos Biológicos/química , Descubrimiento de Drogas/métodos , Informática/métodos , Peptaiboles/química , Antifúngicos/química , Péptidos Catiónicos Antimicrobianos , Hypocrea/química , Espectrometría de Masas , Péptidos/químicaRESUMEN
Streptomyces sp. strain RKCA744 was isolated from sediment collected from the Arauca River, Colombia.